tbuckley/cabot-search huggingface dataset:
Abstract P316: Lower Mortality From Ischemic Heart Disease Associated With Attenuation of Autonomic Dysfunction is Related to Reduction of Sensitivity to Pain at the Chest Bone
Authors: Jens Faber, Christian Selmer, Finn Gyntelberg, Svend Kreimer, Benny Karpatschof, Søren Ballegaard, Aake Hjalmarson, Albert Gjedde
Journal: Circulation (2023)

Introduction: Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD) and has been found also to be related to elevated measures of sensitivity to pain from pressure (PPS) at the sternum. Previously, we found that non-pharmacological intervention by peripheral sensory nerve stimulation, monitored by repeated home-based PPS measurements, consistently was associated with lowered PPS measures. Compared to the general Danish population, the intervention reduced the all-cause mortality in two prospective observations, one of 103 patients with IHD followed for 3 years, and one of 73 patients with stroke followed for 4.5 years. Here, we test if we can reproduce lower all-cause mortality associated with lowered PPS measures in a randomized controlled trial (RCT). Methods: Of 361 consecutively followed patients with stable IHD, 65% had elevated PPS, suggestive of ANSD. Of these, 213 participated in a randomized controlled trial (RCT) with active (n=106) or passive intervention (n=107). We compared the 5-year all-cause mortality of both groups with two corresponding subsections of approximately 35.000 members of the general population of Denmark, matching patients for gender, age, and observation period with data from Statistics Denmark, and we compared the 5-year mortality of the two RCT groups. In separate analyses, we pooled mortality data from the active group of the RCT with data from two observational studies. We registered the pooled active intervention mortality of 1.168 person-years, compared to approximately 40 million person-years of the pooled general population. Results: We observed fewer than three deaths in the active RCT group (exact number and 95% CI not available according to GDRP rules), compared to eight deaths of passive RCT group members (P=0.035). Based on the predicted mortality from the general population of eight deaths in both groups, the result is consistent with significantly reduced mortality of recipients of active intervention (P=0.011). The separate analyses of pooled data from three consecutive studies demonstrated a mean reduction of the 4.2-year all-cause mortality of 50% (P&lt;0.00005). Conclusions: The predicted attenuation of ANSD associated with lowering of elevated PPS matched the lower all-cause mortality of patients with IHD.
Abstract P269: Associations Between Neighborhood Socioeconomic Deprivation During Pregnancy and Offspring Early Anthropometric Outcomes
Authors: Sam Neally, Elizabeth Widen, Cathrine Hoyo, Chantel Martin
Journal: Circulation (2023)

Introduction: Residing in areas with lower neighborhood socioeconomic position (NSEP) is associated with adverse birth outcomes like small for gestational age and low birthweight. Lower NSEP is also associated with higher weight status and blood pressure in adolescence. However, few studies have assessed NSEP and indicators of cardiometabolic health in early childhood. We examined associations between NSEP during gestation and changes in early childhood weight in a North Carolina (NC) birth cohort. Hypothesis: We hypothesized that lower gestational NSEP would associate with rapid infant weight gain and increased odds of having overweight in early childhood. Methods: The sample was from the Newborn Epigenetics STudy (NEST) cohort. 2,681 gestational parent-offspring pairs were recruited from prenatal visits at obstetrics care facilities in Durham County, NC and enrolled between 2005-2011. For this study, offspring were assessed at birth (N=1,058), 6 months (N=1,268), 1 year (N=1,268), 2 years (N=1,033), and 3 years (N=1,038). NSEP was measured as Neighborhood Deprivation Index (NDI) tertiles at the 2010 US census block group level in NC using parent residential address at enrollment (high NDI=low NSEP). Offspring anthropometric outcomes included: (1) having vs not having overweight (weight for length or body mass index percentiles ≥85 th ) at each study visit; and (2) having rapid vs non-rapid infant weight gain from birth to 6 months and birth to 1 year. Multilevel logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for the relationship between NDI (ref=low) and weight, adjusting for gestational parent age, race, marital status, and education. Results: On average, gestational parents were 28 years old with college degrees (35%), followed by high school or equivalent (22%), and identifying as non-Hispanic (NH) Black (43%), followed by NH White (34%). Prior to covariate adjustment, children residing in neighborhoods with high vs low NDI had greater odds of having overweight at 6 months (OR=1.57, 95% CI=1.10-2.25), 1 year (OR=2.01, 95% CI=1.49-2.71), 2 years (OR=1.78, 95% CI=1.25-2.49), and 3 years (OR=1.35, 95% CI=0.96-1.89) and of experiencing rapid infant weight gain from birth to 6 months (OR=1.03, 95% CI=0.79-1.33) and to 1 year (OR=1.62, 95% CI=1.25-2.09). Associations were attenuated after adjustment, but children residing in neighborhoods with high vs low NDI had greater odds of having overweight at 1 year (OR=1.53, 95% CI=1.09-2.15). Conclusions: Low NSEP may associate with higher early childhood weight. This has important implications for later developmental milestones and health outcomes in childhood. Several potential mechanisms could explain this association, including biological programming and limited neighborhood opportunities for movement and healthy eating. Future work exploring these and other mechanisms is warranted.
Abstract P563: Exploring Facility and Patient-Level Determinants of Changes in Systolic Blood Pressure Among Patients With Hypertension: A Multicenter Study in Ghana
Authors: Samuel Byiringiro, Thomas Hinneh, FRED S SARFO, Yvonne Commodore-Mensah, Shadrack Osei Asibey, Cheryl R Dennison Himmelfarb
Journal: Circulation (2023)

Background: Optimal blood pressure control is essential in averting complications and associated cardiovascular risks. Although a 5-mmHg reduction in systolic blood pressure (SBP) is associated with better health outcomes, individual-level and health facility dynamics might influence optimal blood pressure control. We explored individual and health facility-level factors of SBP changes among patients with hypertension in Ghana. Methods: We recruited 15 health facilities that provided hypertension care and from each facility, 15 patients who were currently receiving hypertension care during their clinic appointment. We explored patient-level (adherence to treatment, length of time with hypertension diagnosis, and sociodemographic factors) and health-facility level (accessibility of care, health facility management, bed capacity, provider training, and provider-patient ratio) predictors. We fitted two-level mixed-effect linear regression models to identify predictors of SBP changes. Results: We included 222 patients, 81% were female, and 48% had achieved blood pressure control of &lt; 140/90 mmHg. At the patient level, secondary-level education was associated with a 7.5 mmHg (95% CI: -14.74, -0.28) greater reduction in SBP than a primary or lower level of education (Table). Patients treated at private facilities had on average 15.8 mmHg (95% CI: 4.97, 26.62) higher SBP than those in government health facilities. Patients who were receiving care at health facilities where a physician or physician assistant treated ≥ 280 patients/month had 28.4 mmHg (95% CI: 9.77, 46.97) higher SBP than those receiving care from a physician/physician assistant who cared for &lt; 140 patients/month. Conclusion: Health system interventions to address individual barriers, the shortage of healthcare providers, and team-based care strategies are needed to address the burden of hypertension in Ghana.
Abstract P189: Sexual Minority Status Disparities in Life’s Simple 7 and Life’s Essential 8 Cardiovascular Health Scores, a French Nationwide Population-Based Study
Authors: Omar Deraz, Billy A Caceres, Carl G Streed, Lauren B Beach, Xavier Jouven, Mathilde Touvier, Marcel Goldberg, Marie Zins, Jean-Philippe Empana
Journal: Circulation (2023)

A higher burden of cardiovascular disease risk factors has been reported in sexual minority populations (SM), such as lesbian, gay, bisexual, and non-heterosexual, compared to heterosexual populations. Therefore, primordial prevention, i.e., preventing risk factor onset in the first place, may be a relevant preventative strategy in this population. This study aimed to quantify the associations of SM status in each sex with Life’s Simple 7 (LS7) and Life’s Essential 8 (LE8) cardiovascular health (CVH) scores. The CONSTANCES study is a multicentric study that recruited randomly selected adults in 24 health examination centers in 21 cities in the French European territory. Sexual minority status was based on self-reported lifetime sexual behavior and categorized as lesbian, gay, bisexual, or heterosexual. The study included 169,434 CVD-free participants (53.64% women, mean age: 46.00 years). Among 90879 women, 555 were lesbian, 3149 bisexual, and 84363 heterosexual. Among 78555 men, 2421 were gay, 2748 bisexual, and 70994 heterosexual. Overall, 2812 women and 2392 men declined to answer. In women, the prevalence of high LS7 scores (12-14) ranged from 9.00% (declined to answer) to 12.38% (bisexual), whereas in men, it ranged from 4.06% (declined to answer) to 9.17% (gay). In multivariate analyses (Table 1), lesbian and bisexual women had lower LS7 score compared to heterosexual women. However, this was observed only among those who had never been pregnant (p for interaction &lt;0.05). Conversely, gay and bisexual men living in urban areas had higher LS7 score compared to heterosexual men, while those living in rural areas had lower LS7 score than their heterosexual counterparts (p for interaction &lt;0.05). Findings were consistent when using the LE8 score but with stronger effect sizes (Table 1). This study supports the presence of CVH disparities in sexual minority adults and may help identify vulnerable populations for prioritizing primordial CVD prevention.
Abstract P210: Dietary Calcium and Phosphorus Intakes at Middle Age and Their Associations With Vascular Calcification at Older Age: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yume Nohara-Shitama, Yejin Mok, Shoshana Ballew, Casey M Rebholz, Matthew Budoff, Cheryl Anderson, Junichi Ishigami, Michael Blaha, Kunihiro Matsushita
Journal: Circulation (2023)

Background: High dietary calcium and phosphorus intakes may accelerate vascular calcification. A few studies have explored the association of dietary calcium and phosphorus intakes with vascular calcification but reported inconsistent results. Most studies relied on dietary assessment at one time point and evaluated only coronary artery calcification. Aim: To assess the associations of dietary calcium and phosphorus intakes over two time points during middle age with coronary artery and extra-coronary calcification at older age. Methods: We studied 1,940 ARIC participants who underwent chest CT scans at ≥75 years of age in 2018-19 and completed a 66-item food frequency questionnaire at two earlier visits (1987-89 and 1993-95). We calculated the average of dietary calcium and phosphorus intakes across these two visits. Calcification was quantified as Agatston score in coronary arteries, ascending aorta, descending aorta, aortic valve ring, aortic valve, and mitral valve. We ran multivariable linear (for continuous Agatston score) and logistic regression models (for Agatston score &gt;75 th percentile). Results: The mean dietary calcium and phosphorus intake was 659 mg/day and 1,074 mg/day, respectively. Overall, we did not observe any positive associations of dietary calcium intake with vascular/valvular calcification. Rather, we saw its inverse association with ascending aorta calcification (Figure). In contrast, dietary phosphorus was not associated with the calcification of any vascular beds. The results were largely similar in linear regression models and after excluding 332 participants (17%) taking calcium supplements. Conclusion: Dietary calcium intake at middle age was largely neutral in its association with vascular calcification while showing a mild inverse association with ascending aorta calcification at older age. No evident associations were seen for dietary phosphorus. Our findings do not support a concern that a calcium or phosphorus-rich diet may accelerate vascular calcification.
Abstract 06: Discrimination Experiences and All-Cause and Cardiovascular Mortality: The Multi-Ethnic Study of Atherosclerosis
Authors: Wayne R Lawrence, Gieira S Jones, Jarrett A Johnson, Koya P Ferrell, Jacquita N Johnson, Meredith S Shiels, Ana V Diez Roux, Allana T Forde
Journal: Circulation (2023)

Introduction: Epidemiologic studies have documented the associations between experiences of discrimination and adverse health outcomes. However, the relationship between discrimination and mortality, and the factors that may moderate this relationship are not well understood. This study examined whether lifetime and everyday discrimination were associated with all-cause and cardiovascular mortality, and whether these associations differed by race/ethnicity, gender, and racial/ethnic residential segregation. Hypothesis: We hypothesized that greater exposure to lifetime and everyday discrimination would be associated with increased risk of cardiovascular mortality, and that these associations would be modified by race/ethnicity, gender, and racial/ethnic residential segregation. Methods: The study included 1,633 Black, 1,403 Hispanic/Latino, and 2,473 White participants aged 45 to 84 years from the Multi-Ethnic Study of Atherosclerosis, enrolled from 2000-2002 and followed across 5 exams (2002-2018). In addition to exams, follow-up for mortality involved phone calls and linkage with the National Death Index. Discrimination was measured using the lifetime discrimination (major experiences of unfair treatment) and everyday discrimination (day-to-day experiences of unfair treatment) scales. Racial/ethnic residential segregation was measured using the Gi* statistic. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs), adjusting for sociodemographic characteristics, health behaviors, and clinical risk factors. Results: Each increase in reports of lifetime discrimination was associated with increased all-cause (HR=1.06; 95%CI 1.00,1.11,) and cardiovascular (HR=1.15; 95%CI 1.04, 1.27) mortality, adjusting for sociodemographic factors, health behaviors, and clinical risk factors. Associations between lifetime discrimination and cardiovascular mortality were observed across all racial/ethnic groups but were strongest and only statistically significant among Black participants (HR=1.18; 95%CI 1.02, 1.37). Additionally, in the fully adjusted model, each increase in reports of everyday discrimination was marginally associated with increased all-cause mortality (HR=1.07; 95%CI 0.98-1.17) and strongly associated with increased cardiovascular mortality (HR=1.21; 95%CI 1.03, 1.43). Associations for lifetime and everyday discrimination with all-cause and cardiovascular mortality were not modified by race/ethnicity, gender, or racial/ethnic residential segregation. Conclusion: These findings suggest that experiences of discrimination are associated with increased all-cause and cardiovascular mortality. Our results underscore the need for interventions aimed at preventing and mitigating the adverse health effects of discrimination.
Abstract P168: Early Life Metal Profiles and Kidney Function in Mid-Adolescence: A Preliminary Study in Project Viva
Authors: Pi-i D Lin, Andres Cardenas, Sheryl L Rifas-Shiman, Ami R Zota, Marie-France Hivert, Emily Oken, Izzuddin M Aris, Alison P Sanders
Journal: Circulation (2023)

Introduction: The developing kidney is vulnerable to pre- and postnatal environmental stressors. Suboptimal environmental conditions during early life, such as exposure to toxic metals and deficiency in essential metals, can alter the risk of kidney dysfunction later in life. In this pilot study, we aimed to examine the relationship between prenatal exposure to metals and adolescent kidney function using data from Project Viva, a Boston-area prospective pre-birth cohort. Hypothesis: Prenatal exposure to higher metal concentrations, both individually and as mixtures, will be associated with altered kidney function in mid-adolescence. Methods: We assessed the following metals in erythrocyte samples collected during pregnancy: 1 st -trimester [arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), mercury (Hg), lead (Pb), copper (Cu), magnesium (Mg), manganese (Mn), selenium (Se), and Zinc (Zn)]; 2 nd -trimester (Pb, Mn, Hg, and Se). We measured plasma cystatin C and creatinine from blood samples collected in mid-adolescence (mean age 18 years) in a sub-sample of Project Viva participants. We calculated the estimated glomerular filtrate rate (eGFR) using a cystatin C-based equation for children. We examined associations of prenatal metal exposure and mid-adolescent eGFR using linear regression for single metal analyses, and Bayesian kernel machine regression and quantile-based g-computation for mixture analyses. In all models, we adjusted for maternal education level, annual household income, race/ethnicity, child sex, and age at eGFR assessment. Results: A total of 146 participants had complete data for 1 st -trimester erythrocyte metals and mid-adolescent eGFR, and 105 participants had complete data for 2 nd -trimester blood metals and mid-adolescent eGFR. All children had eGFR values in the normal range (i.e., &gt;60 mL/min/1.73m 2 ); the mean (SD) eGFR was 92.0 (13.7) mL/min/1.73m 2 . Most pairwise metal-eGFR relationships were statistically null; however, a 2-fold increase in 1 st -trimester Zn was associated with higher eGFR (β 7.25 mL/min/1.73m 2 ; 95% CI 0.33, 14.16), while a 2-fold increase in 2 nd -trimester Pb was associated with lower eGFR (β -4.90 mL/min/1.73m 2 ; 95% CI -8.32, -1.48). Mixture analyses did not identify statistically significant findings but suggested some non-linear associations and interactions between metals. Conclusions: Preliminary evidence suggests that prenatal Zn exposure is associated with higher kidney function while prenatal Pb exposure is associated with lower kidney function in mid-adolescence. We plan to assess eGFR in additional participants to increase the power of the analyses.
Abstract P454: Secular Trend in Cholesterol Management Among US Veterans With ASCVD
Authors: Awsse Al-Ani, Helen Wellman, Rachel Ward, John M Gaziano, Luc Djousse
Journal: Circulation (2023)

Background: Current guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) have explicitly highlighted the direct correlation of reduced LDL-C with a subsequent risk reduction in further ischemic events. Little is known about secular trends of LDL-cholesterol below 70 mg/ml among Veterans with ASCVD over the past two decades. Hypothesis: Among Veterans with ASCVD who are receiving lipid-lowering therapy, the proportion of those not treated to goal (LDL-C ≥70 mg/dL) has been declining between 2002 and 2020. Methods: We conducted a retrospective cohort study with an annual accounting of treatment information and LDL-C lab results between 2003 to 2020 for US Veterans with prevalent ASCVD who had at least one LDL-C lab value during the year prior to January 1st of the index year. Dyslipidemia was defined as LDL-C ≥70 mg/dL and ASCVD was defined as one inpatient or two outpatient diagnoses or one procedure diagnosis for MI, stroke, CAD, PAD, or angina. We investigated annual trends in proportion of Veterans with ASCVD who achieved LDL-C&lt;70 mg/dL using lipid-lowering agents. Results: The study population consisted of 1,182,657 Veterans with a mean age of 72.5 years, 97% male, and a mean BMI of 29.8 kg/m 2 . The mean LDL-C in 2003 was 84.7 mg/dl and 739,295 (62.5%) participants had an LDL-C ≥70 mg/dl. We observed a steady increase in the proportion of Veterans achieving LDL below 70 mg/dl during the study period (Figure). Conclusion: Our data are consistent with a steady increase in proportion of US Veterans with ASCVD with LDL treated to goal between 2003 and 2020.
Abstract MP21: Associations Between Plasma Proteome, Leukocyte Telomere Length, and Polygenic Risk Score for Leukocyte Telomere Length: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Aixin Li, Ingrid Jacobson, Brian T Steffen, Jiaqi Xie, Nathan Pankratz, John Lane, Dan E Arking, Thomas Mosley, Weihua Guan, Sanaz Sedaghat, Jim S Pankow, Pamela L Lutsey, Weihong Tang
Journal: Circulation (2023)

Introduction: Leukocyte telomere length (LTL) is an important aging biomarker implicated in the pathogenesis of age-related conditions. We conducted a large-scale proteomics study to characterize the proteomic signatures of LTL and its genetic determinants measured by polygenic risk score (PRS). Hypothesis: We hypothesize that LTL and LTL PRS are associated with blood proteomic signatures linked to aging-related conditions. Methods: We used TelSeq to estimate LTL based on whole genome sequencing (WGS) data measured in samples collected in ARIC visits 1, 2, and 3 (i.e., the baseline for this study). TelSeq counted reads containing at least 12 TTAGGG repeats. This count was then normalized to the number of reads with GC content between 48% and 52%. Only samples with read lengths of 150 or 151 were included in subsequent analyses, and LTL estimates were inverse normalized within read length group and WGS group before being merged. We derived a PRS for LTL based on previously published genome-wide association study (GWAS) summary statistics for 150 significant autosomal SNPs and ARIC GWAS data. We then analyzed LTL or LTL PRS as a predictor and plasma levels of proteins as outcomes, measured at ARIC visit 2 (for the LTL PRS analysis) and visit 3 (for the LTL analysis) using SOMAscan v4 (~5,000 proteins). Race-specific linear regressions were performed to evaluate the association between LTL or LTL PRS and levels of each protein adjusting for potential confounders at baseline. We used a Bonferroni correction to account for multiple testing. The analysis in Whites served as a discovery (p≤1x10 -5 ) and that in Blacks as a replication. Results: The final sample sizes were as follows: LTL PRS analysis (n=7,587 Whites and 2,094 Blacks) and LTL analysis (n=5,014 Whites and 884 Blacks). In Whites, LTL PRS was significantly associated with five proteins (p≤1x10 -5 ) that also showed the same direction of association in Blacks: THPO, GP1Bα, PEAR1, KDR, and GP5, with the association for KDR reaching nominal significance in Blacks (p=0.02). For LTL as the predictor, GP1Bα, GDF15 and TXNDC5 were significant in Whites, with consistent direction of associations in Blacks (p&gt;0.05). These proteins are linked to hemostasis (all), endothelial proliferation (KDR), heart disease and cancer (GDF15), and cancer and rheumatoid arthritis (TXNDC5) in the literature. Conclusion: This large-scale proteomic analysis reveals blood proteomic signatures for LTL PRS and LTL, which will likely improve the understanding of biological pathways and clinical conditions implicated by LTL.